A.U. College of Pharmaceutical Sciences, Andhra University, Visakhapatnam, 530003, India.
School of Pharmacy, University of Botswana, Gaborone, Private bag-0022, Botswana.
Neurochem Int. 2022 May;155:105311. doi: 10.1016/j.neuint.2022.105311. Epub 2022 Feb 23.
Mechanistic/mammalian target of rapamycin (mTOR) belongs to the phosphatidylinositol kinase-related kinase (PIKK) family. mTOR signaling is required for the commencement of essential cell functions including autophagy. mTOR primarily governs cell growth in response to favourable nutrients and other growth stimuli. However, it also influences aging and other aspects of nutrient-related physiology such as protein synthesis, ribosome biogenesis, and cell proliferation in adults with very limited growth. The major processes for survival such as synaptic plasticity, memory storage and neuronal recovery involve a significant mTOR activity. mTOR dysregulation is becoming a prevalent motif in a variety of human diseases, including cancer, neurological disorders, and other metabolic syndromes. The use of rapamycin to prolong life in different animal models may be attributable to the multiple roles played by mTOR signaling in various processes involved in ageing, protein translation, autophagy, stem cell pool turnover, inflammation, and cellular senescence. mTOR activity was found to be altered in AD brains and rodent models, supporting the notion that aberrant mTOR activity is one of the key events contributing to the onset and progression of AD hallmarks This review assesses the molecular association between the mTOR signaling pathway and pathogenesis of Alzheimer's disease. The research data supporting this theme are also reviewed.
机械/哺乳动物雷帕霉素靶蛋白（mTOR）属于磷脂酰肌醇激酶相关激酶（PIKK）家族。mTOR 信号通路对于启动包括自噬在内的基本细胞功能是必需的。mTOR 主要通过响应有利的营养物质和其他生长刺激来控制细胞生长。然而，它也影响衰老和其他与营养相关的生理方面，如蛋白质合成、核糖体生物发生和成年人的细胞增殖，而这些方面的生长非常有限。存活的主要过程，如突触可塑性、记忆存储和神经元恢复，都涉及到显著的 mTOR 活性。mTOR 失调正在成为多种人类疾病的普遍特征，包括癌症、神经紊乱和其他代谢综合征。雷帕霉素用于延长不同动物模型的寿命，可能归因于 mTOR 信号在涉及衰老、蛋白质翻译、自噬、干细胞池更新、炎症和细胞衰老的各种过程中所起的多种作用。在 AD 大脑和啮齿动物模型中发现 mTOR 活性发生改变，支持了异常的 mTOR 活性是导致 AD 特征性疾病发生和进展的关键事件之一的观点。本综述评估了 mTOR 信号通路与阿尔茨海默病发病机制之间的分子关联，并对支持这一主题的研究数据进行了综述。
